tbuckley/cabot-search huggingface dataset:
Depletion of Conventional Type-1 Dendritic Cells in Established Tumors Suppresses Immunotherapy Efficacy
Authors: Alvaro Teijeira, Saray Garasa, Carlos Luri-Rey, Carlos de Andrea, Maria Gato, Carmen Molina, Tsuneyasu Kaisho, Assunta Cirella, Arantza Azpilikueta, Steffanie K. Wculek, Josune Egea, Irene Olivera, Inmaculada Rodriguez, Ana Rouzaut, Vladislav Verkhusha, Karmele Valencia, David Sancho, Pedro Berraondo, Ignacio Melero
Journal: Cancer Research (2022)

Abstract The ability of conventional type-1 dendritic cells (cDC1) to cross-present tumor antigens to CD8+ T cells is critical for the induction of antitumor CTLs. Mice that are constitutively deficient in cDC1 cells have been reported to fail to respond to immunotherapy strategies based on checkpoint inhibitors. However, further work is needed to clarify the precise time during immunotherapy treatment that cDC1 cells are required for the beneficial effect of treatment. Here, we used a refined XCR1-DTR-Venus transgenic mouse model to acutely deplete cDC1 cells and trace their behavior using intravital microscopy. Diphtheria toxin–mediated cDC1 depletion prior to immunotherapy treatment with anti–PD-1 and/or anti-CD137 immunostimulatory mAbs completely ablated antitumor efficacy. The efficacy of adoptive T-cell therapy was also hampered by prior cDC1 depletion. After the onset of immunotherapy treatment, depletion of cDC1s only moderately reduced the therapeutic efficacy of anti–PD-1 and anti-CD137 mAbs. Intravital microscopy of liver-engrafted tumors revealed changes in the intratumoral behavior of cDC1 cells in mice receiving immunotherapy, and treatment with diphtheria toxin to deplete cDC1s impaired tumor T-cell infiltration and function. These results reveal that the functional integrity of the cDC1 compartment is required at the onset of various immunotherapies to successfully treat established tumors. Significance: These findings reveal the intratumoral behavior of cDC1 dendritic cells in transgenic mouse models and demonstrate that the efficacy of immunotherapy regimens is precluded by elimination of these cells.
Genetic Variants of the COL4A3, COL4A4, and COL4A5 Genes Contribute to Thinned Glomerular Basement Membrane Lesions in Sporadic IgA Nephropathy Patients
Authors: Xiaohan Yuan, Qing Su, Hui Wang, Sufang Shi, Lijun Liu, Jicheng Lv, Suxia Wang, Li Zhu, Hong Zhang
Journal: Journal of the American Society of Nephrology (2022)

Thinned glomerular basement membrane (tGBM) lesions are not uncommon in IgA nephropathy (IgAN). Type IV collagen-built of α 3, α 4, and α 5 chains, encoded by COL4A3 / COL4A4 / COL4A5 genes-is the major component of glomerular basement membrane (GBM). In recent years, mutations in type IV collagen-encoding genes were also reported in patients with a histologic diagnosis of FSGS. Pathogenic COL4A3 / COL4A4 / COL4A5 variants were recently identified in familial cases of IgAN, but the contribution of these variants to sporadic IgAN is still unclear.
Sleep exerts lasting effects on hematopoietic stem cell function and diversity
Authors: Cameron S. McAlpine, Máté G. Kiss, Faris M. Zuraikat, David Cheek, Giulia Schiroli, Hajera Amatullah, Pacific Huynh, Mehreen Z. Bhatti, Lai-Ping Wong, Abi G. Yates, Wolfram C. Poller, John E. Mindur, Christopher T. Chan, Henrike Janssen, Jeffrey Downey, Sumnima Singh, Ruslan I. Sadreyev, Matthias Nahrendorf, Kate L. Jeffrey, David T. Scadden, Kamila Naxerova, Marie-Pierre St-Onge, Filip K. Swirski
Journal: The Journal of Experimental Medicine (2022)

A sleepless night may feel awful in its aftermath, but sleep's revitalizing powers are substantial, perpetuating the idea that convalescent sleep is a consequence-free physiological reset. Although recent studies have shown that catch-up sleep insufficiently neutralizes the negative effects of sleep debt, the mechanisms that control prolonged effects of sleep disruption are not understood. Here, we show that sleep interruption restructures the epigenome of hematopoietic stem and progenitor cells (HSPCs) and increases their proliferation, thus reducing hematopoietic clonal diversity through accelerated genetic drift. Sleep fragmentation exerts a lasting influence on the HSPC epigenome, skewing commitment toward a myeloid fate and priming cells for exaggerated inflammatory bursts. Combining hematopoietic clonal tracking with mathematical modeling, we infer that sleep preserves clonal diversity by limiting neutral drift. In humans, sleep restriction alters the HSPC epigenome and activates hematopoiesis. These findings show that sleep slows decay of the hematopoietic system by calibrating the hematopoietic epigenome, constraining inflammatory output, and maintaining clonal diversity.
Right ventricular–pulmonary arterial coupling and its relationship to exercise haemodynamics in a continuum of patients with pulmonary vascular disease due to chronic thromboembolism
Authors: Philipp Douschan, Khodr Tello, Andreas J. Rieth, Christoph B. Wiedenroth, Teresa Sassmann, Gabor Kovacs, Hossein A. Ghofrani, Werner Seeger, Manuel Richter, Stefan Guth
Journal: European Respiratory Journal (2022)

<b>This retrospective study shows that TAPSE/sPAP ratio, a simple surrogate of RV–PA coupling, may help to identify patients with PVD due to chronic thromboembolism and predicts impaired pulmonary exercise haemodynamics</b>https://bit.ly/3osXxzV
Living without eosinophils: evidence from mouse and man
Authors: David J. Jackson, Ian D. Pavord
Journal: European Respiratory Journal (2022)

The enduring view of eosinophils, as immune effector cells whose primary function is host defence against infection by helminths and other microbial pathogens, sets the stage for a fundamental question regarding the safety of therapeutic eosinophil depletion. If eosinophils are significantly reduced or altogether depleted in an effort to alleviate the negative effects of tissue eosinophilia and eosinophilic inflammation in conditions such as asthma, COPD, chronic rhinosinusitis with nasal polyps, eosinophilic granulomatosis with polyangiitis and hypereosinophilic syndrome, would these patients become susceptible to infection or another illness? Development of mouse models in which the eosinophil lineage has been ablated, observations in patients naturally lacking eosinophils and data from studies of eosinophil-depleting medical therapies indicate that the absence of eosinophils is not detrimental to health. The evidence available to date, as presented in this review, supports the conclusion that even if certain homeostatic roles for the eosinophil may be demonstrable in controlled animal models and human in vitro settings, the evolution of the human species appears to have provided sufficient immune redundancy such that one may be hale and hearty without eosinophils.
Zinc finger protein 33B demonstrates sex interaction with atopy-related markers in childhood asthma
Authors: Sanghun Lee, Dmitry Prokopenko, Rachel S. Kelly, Sharon Lutz, Jessica Ann Lasky-Su, Michael H. Cho, Cecelia Laurie, Juan C. Celedón, Christoph Lange, Scott T. Weiss, Julian Hecker, Dawn L. DeMeo
Journal: European Respiratory Journal (2022)

Background Sex differences related to immune responses can influence atopic manifestations in childhood asthma. While genome-wide association studies have investigated a sex-specific genetic architecture of the immune response, gene-by-sex interactions have not been extensively analysed for atopy-related markers including allergy skin tests, IgE and eosinophils in asthmatic children. Methods We performed a genome-wide gene-by-sex interaction analysis for atopy-related markers using whole-genome sequencing data based on 889 trios from the Genetic Epidemiology of Asthma in Costa Rica Study (GACRS) and 284 trios from the Childhood Asthma Management Program (CAMP). We also tested the findings in UK Biobank participants with self-reported childhood asthma. Furthermore, downstream analyses in GACRS integrated gene expression to disentangle observed associations. Results Single nucleotide polymorphism (SNP) rs1255383 at 10q11.21 demonstrated a genome-wide significant gene-by-sex interaction (p interaction =9.08×10 −10 ) for atopy (positive skin test) with opposite direction of effects between females and males. In the UK Biobank participants with a history of childhood asthma, the signal was consistently observed with the same sex-specific effect directions for high eosinophil count (p interaction =0.0058). Gene expression of ZNF33B (zinc finger protein 33B), located at 10q11.21, was moderately associated with atopy in girls, but not in boys. Conclusions We report SNPs in/near a zinc finger gene as novel sex-differential loci for atopy-related markers with opposite effect directions in females and males. A potential role for ZNF33B should be studied further as an important driver of sex-divergent features of atopy in childhood asthma.
Therapeutic perspectives on father-daughter incest
Authors: Lisa Swanson, Mary K. Biaggio
Journal: American Journal of Psychiatry (1985)

In recent years it has become apparent that father-daughter incest is not an uncommon occurrence. Many social forces have conspired to maintain secrecy at both the family and societal levels. The authors examine the evolution of professional attitudes and understandings of incest, beginning with Freud's writings on the subject, and offer specific recommendations for clinicians working with incest victims and their families.
Does repeated influenza vaccination attenuate effectiveness? A systematic review and meta-analysis
Authors: Elenor Jones-Gray, Elizabeth J Robinson, Adam J Kucharski, Annette Fox, Sheena G Sullivan
Journal: The Lancet Respiratory Medicine (2022)

Influenza vaccines require annual readministration; however, several reports have suggested that repeated vaccination might attenuate the vaccine's effectiveness. We aimed to estimate the reduction in vaccine effectiveness associated with repeated influenza vaccination.
Impaired immune response drives age-dependent severity of COVID-19
Authors: Julius Beer, Stefania Crotta, Angele Breithaupt, Annette Ohnemus, Jan Becker, Benedikt Sachs, Lisa Kern, Miriam Llorian, Nadine Ebert, Fabien Labroussaa, Tran Thi Nhu Thao, Bettina Salome Trueeb, Joerg Jores, Volker Thiel, Martin Beer, Jonas Fuchs, Georg Kochs, Andreas Wack, Martin Schwemmle, Daniel Schnepf
Journal: The Journal of Experimental Medicine (2022)

Severity of COVID-19 shows an extraordinary correlation with increasing age. We generated a mouse model for severe COVID-19 and show that the age-dependent disease severity is caused by the disruption of a timely and well-coordinated innate and adaptive immune response due to impaired interferon (IFN) immunity. Aggravated disease in aged mice was characterized by a diminished IFN-γ response and excessive virus replication. Accordingly, adult IFN-γ receptor-deficient mice phenocopied the age-related disease severity, and supplementation of IFN-γ reversed the increased disease susceptibility of aged mice. Further, we show that therapeutic treatment with IFN-λ in adults and a combinatorial treatment with IFN-γ and IFN-λ in aged Ifnar1−/− mice was highly efficient in protecting against severe disease. Our findings provide an explanation for the age-dependent disease severity and clarify the nonredundant antiviral functions of type I, II, and III IFNs during SARS-CoV-2 infection in an age-dependent manner. Our data suggest that highly vulnerable individuals could benefit from immunotherapy combining IFN-γ and IFN-λ.
Sex differences in clinical outcomes and biological profiles in systemic sclerosis-associated interstitial lung disease: a post-hoc analysis of two randomised controlled trials
Authors: Elizabeth R Volkmann, Donald P Tashkin, Richard Silver, Carol Feghali Bostwick, Shervin Assassi, DeAnna Baker Frost, Mei Leng, Holly Wilhalme, Grace Hyun Kim, Jonathan Goldin, Michael D Roth
Journal: The Lancet Rheumatology (2022)
Safety and tolerability of nintedanib in patients with interstitial lung diseases in subgroups by sex: a post-hoc analysis of pooled data from four randomised controlled trials
Authors: Anna-Maria Hoffmann-Vold, Elizabeth R Volkmann, Yannick Allanore, Shervin Assassi, Jeska K de Vries-Bouwstra, Vanessa Smith, Inga Tschoepe, Lazaro Loaiza, Madhu Kanakapura, Oliver Distler
Journal: The Lancet Rheumatology (2022)
Women in rheumatology in Africa
Authors: Dzifa Dey, Farhanah Paruk, Girish M Mody, Asgar A Kalla, Adewale Adebajo, Akpabio Akpabio, Mohammed Hassan Abu-Zaid, Riëtte du Toit, Madeleine Ngandeu-Singwe, Uhunmwangho U Courage, Ouma Devi Koussougbo, Angela Migowa, Farzana Moosajee, Rakotomalala Hoby Nomena, Hakeem B Olaosebikan, Elisa Palalane, Pierrot Litite Lebughe, Hela Sahli, Landry Missounga Cames, Diomandé Mohamed, Souhaibou Ndongo, Cissé Idrissa, Ihsane Hmamouchi
Journal: The Lancet Rheumatology (2022)
Protection against omicron (B.1.1.529) BA.2 reinfection conferred by primary omicron BA.1 or pre-omicron SARS-CoV-2 infection among health-care workers with and without mRNA vaccination: a test-negative case-control study
Authors: Sara Carazo, Danuta M Skowronski, Marc Brisson, Sapha Barkati, Chantal Sauvageau, Nicholas Brousseau, Rodica Gilca, Judith Fafard, Denis Talbot, Manale Ouakki, Vladimir Gilca, Alex Carignan, Geneviève Deceuninck, Philippe De Wals, Gaston De Serres
Journal: The Lancet Infectious Diseases (2022)
Multifunctional light-activatable nanocomplex conducting temperate-heat photothermal therapy to avert excessive inflammation and trigger augmented immunotherapy
Authors: Lu Li, Xiuqi Liang, Tao He, Xinchao Li, Xianzhou Huang, Ning Wang, Meiling Shen, Yaqian Shu, Rui Wu, Miaomiao Zhang, Qinjie Wu, Changyang Gong
Journal: Biomaterials (2022)
A novel approach for the prevention of ionizing radiation-induced bone loss using a designer multifunctional cerium oxide nanozyme
Authors: Fei Wei, Craig J. Neal, Tamil Selvan Sakthivel, Yifei Fu, Mahmoud Omer, Amitava Adhikary, Samuel Ward, Khoa Minh Ta, Samuel Moxon, Marco Molinari, Jackson Asiatico, Michael Kinzel, Sergey N. Yarmolenko, Vee San Cheong, Nina Orlovskaya, Ranajay Ghosh, Sudipta Seal, Melanie Coathup
Journal: Bioactive Materials (2022)

The disability, mortality and costs due to ionizing radiation (IR)-induced osteoporotic bone fractures are substantial and no effective therapy exists. Ionizing radiation increases cellular oxidative damage, causing an imbalance in bone turnover that is primarily driven via heightened activity of the bone-resorbing osteoclast. We demonstrate that rats exposed to sublethal levels of IR develop fragile, osteoporotic bone. At reactive surface sites, cerium ions have the ability to easily undergo redox cycling: drastically adjusting their electronic configurations and versatile catalytic activities. These properties make cerium oxide nanomaterials fascinating. We show that an engineered artificial nanozyme composed of cerium oxide, and designed to possess a higher fraction of trivalent (Ce3+) surface sites, mitigates the IR-induced loss in bone area, bone architecture, and strength. These investigations also demonstrate that our nanozyme furnishes several mechanistic avenues of protection and selectively targets highly damaging reactive oxygen species, protecting the rats against IR-induced DNA damage, cellular senescence, and elevated osteoclastic activity in vitro and in vivo. Further, we reveal that our nanozyme is a previously unreported key regulator of osteoclast formation derived from macrophages while also directly targeting bone progenitor cells, favoring new bone formation despite its exposure to harmful levels of IR in vitro. These findings open a new approach for the specific prevention of IR-induced bone loss using synthesis-mediated designer multifunctional nanomaterials.
Effects of tirzepatide versus insulin glargine on kidney outcomes in type 2 diabetes in the SURPASS-4 trial: post-hoc analysis of an open-label, randomised, phase 3 trial
Authors: Hiddo J L Heerspink, Naveed Sattar, Imre Pavo, Axel Haupt, Kevin L Duffin, Zhengyu Yang, Russell J Wiese, Katherine R Tuttle, David Z I Cherney
Journal: The Lancet Diabetes & Endocrinology (2022)
Sex-specific risk of anti-topoisomerase antibodies on mortality and disease severity in systemic sclerosis: 10-year analysis of the Leiden CCISS and EUSTAR cohorts
Authors: Sophie I E Liem, Maaike Boonstra, Saskia le Cessie, Antonella Riccardi, Paolo Airo, Oliver Distler, Marco Matucci-Cerinic, Cristian Caimmi, Elise Siegert, Yannick Allanore, Tom W J Huizinga, René E M Toes, Hans U Scherer, Jeska K de Vries-Bouwstra
Journal: The Lancet Rheumatology (2022)
Food Insecurity Among People With Cancer: Nutritional Needs as an Essential Component of Care
Authors: Margaret Raber, Ann Jackson, Karen Basen-Engquist, Cathy Bradley, Shonta Chambers, Francesca M Gany, Chanita Hughes Halbert, Stacy Tessler Lindau, Rafael Pérez-Escamilla, Hilary Seligman
Journal: JNCI Journal of the National Cancer Institute (2022)

A cancer diagnosis can upend work and family life, leading patients to reallocate resources away from essentials such as food. Estimates of the percentage of people navigating a cancer diagnosis and food insecurity range between 17% and 55% of the cancer patient population. The complexity of addressing food insecurity among those diagnosed with cancer during different phases of treatment is multifactorial and often requires an extensive network of support throughout each phase. This commentary explores the issue of food insecurity in the context of cancer care, explores current mitigation efforts, and offers a call to action to create a path for food insecurity mitigation in the context of cancer. Three programs that address food insecurity among those with cancer at various stages of care are highlighted, drawing attention to current impact and actionable recommendations to make programs like these scalable and sustainable. Recommendations are grounded in the National Academies of Sciences, Engineering, and Medicine social care framework through 5 essential domain areas: awareness, adjustment, assistance, alignment, and advocacy. This commentary seeks to highlight opportunities for the optimization of cancer care and reframe food access as an essential part of treatment and long-term care plans.
Addressing Transportation Insecurity Among Patients With Cancer
Authors: Evan M Graboyes, Krisda H Chaiyachati, Jennifer Sisto Gall, Wenora Johnson, Jerry A Krishnan, Sapna S McManus, Letitia Thompson, Lawrence N Shulman, K Robin Yabroff
Journal: JNCI Journal of the National Cancer Institute (2022)

Health-care-related transportation insecurity is common in the United States. Patients with cancer are especially vulnerable because cancer care is episodic in nature, occurs over a prolonged period, is marked by frequent clinical encounters, requires intense treatments, and results in substantial financial hardship. As a result of transportation insecurity, patients with cancer may forego, miss, delay, alter, and/or prematurely terminate necessary care. Limited data suggest that these alterations in care have the potential to increase the rates of cancer recurrence and mortality and exacerbate disparities in cancer incidence, severity, and outcomes. Transportation insecurity also negatively impacts at the informal caregiver, provider, health system, and societal levels. Recognizing that transportation is a critical determinant of outcomes for patients with cancer, there are ongoing efforts to develop evidence-based protocols to identify at-risk patients and address transportation insecurity at federal policy, health system, not-for-profit, and industry levels. In 2021, the National Cancer Policy Forum of the National Academies of Science, Engineering, and Medicine sponsored a series of webinars addressing key social determinants of health including food, housing, and transportation among patients with cancer. This commentary summarizes the formal presentations and discussions related to transportation insecurity and will 1) discuss the heterogeneous nature of transportation insecurity among patients with cancer; 2) characterize its prevalence along the cancer continuum; 3) examine its multilevel consequences; 4) discuss measurement and screening tools; 5) highlight ongoing efforts to address transportation insecurity; 6) suggest policy levers; and 7) outline a research agenda to address critical knowledge gaps.
Housing Insecurity Among Patients With Cancer
Authors: Qinjin Fan, Danya E Keene, Matthew P Banegas, Sarah Gehlert, Laura M Gottlieb, K Robin Yabroff, Craig E Pollack
Journal: JNCI Journal of the National Cancer Institute (2022)

Abstract Social determinants of health are the economic and environmental conditions under which people are born, live, work, and age that affect health. These structural factors underlie many of the long-standing inequities in cancer care and outcomes that vary by geography, socioeconomic status, and race and ethnicity in the United States. Housing insecurity, including lack of safe, affordable, and stable housing, is a key social determinant of health that can influence—and be influenced by—cancer care across the continuum, from prevention to screening, diagnosis, treatment, and survivorship. During 2021, the National Cancer Policy Forum of the National Academies of Science, Engineering, and Medicine sponsored a series of webinars addressing social determinants of health, including food, housing, and transportation insecurity, and their associations with cancer care and patient outcomes. This dissemination commentary summarizes the formal presentations and panel discussions from the webinar devoted to housing insecurity. It provides an overview of housing insecurity and health care across the cancer control continuum, describes health system interventions to minimize the impact of housing insecurity on patients with cancer, and identifies challenges and opportunities for addressing housing insecurity and improving health equity. Systematically identifying and addressing housing insecurity to ensure equitable access to cancer care and reduce health disparities will require ongoing investment at the practice, systems, and broader policy levels.